Lolamicin is synthesized in five steps. Initially, methyl 3-hydroxybenzoate undergoes
nucleophilic substitution with 3-(chloromethyl)benzonitrile in the presence of potassium carbonate, forming the corresponding ether. The ester is then hydrolyzed under basic conditions to yield the carboxylic acid. In a two-step process, the carboxylic acid is activated using
PyBOP and reacted with N,O-dimethyl hydroxylamine hydrochloride to form the corresponding methoxamide. This intermediate is then subjected to condensation with 2,4,6-collidine under low-temperature conditions using
lithium diisopropylamide (LDA), yielding a dimethylpyridine derivative. Finally, treatment with hydrazine monohydrate under reflux promotes cyclization to produce the final pyridine-pyrazole core structure of lolamicin. ==References==